The present invention relates to compositions, methods, and apparatus that facilitate the performance of diagnostic and therapeutic medical and surgical procedures, such as cardiac surgical procedures, including minimally invasive coronary bypass surgery.
Heart attacks and angina pectoris (chest pain) are caused by occlusions in the coronary arteries. Atherosclerosis, the major cause of coronary artery occlusions, is characterized by deposits of fatty substances, cholesterol, calcium and fibrin within the arterial wall. As the coronary arteries narrow, blood flow is reduced depriving the heart of much needed oxygen. This occurrence is called myocardial ischemia. Severe and prolonged myocardial ischemia produces irreparable damage to the heart muscle, pronounced cardiac dysfunction, and possibly death. Apart from medical therapy, atherosclerosis is treated with coronary artery bypass graft surgery (CABG), percutaneous transluminal coronary angioplasty (PTCA), stents, atherectomy, and transmyocardial laser revascularization (TMLR).
In patients where PTCA, stents, and atherectomy are unsuitable or unsuccessful, CABG is the procedure of choice. In the conventional CABG operation, a long vertical incision is made in the chest, the sternum is split longitudinally and the halves are spread apart to provide access to the heart. Two large bore tubes, or cannulas, are then inserted directly into the right atrium and the aorta in order to establish cardiopulmonary bypass (CPB). The aorta is occluded with an external clamp placed proximal to the aortic cannula. A third cannula is inserted proximal to the aortic clamp, and is used for the delivery of a cardioplegic solution into the coronary arteries. The hyperkalemic cardioplegic solution protects the heart by stopping atrial and ventricular contraction, thereby reducing its metabolic demand. When the heart is not beating, blood flow to the rest of the body is provided by means of CPB. Cardiopulmonary bypass involves removing deoxygenated blood through the cannula in the right atrium, infusing the blood with oxygen, and then returning it through the cannula in the aorta to the patient. With the heart motionless, the surgeon augments blood flow to the ischemic heart muscle by redirecting blood around the coronary artery occlusion. Although there are several methods to bypass an occlusion, the most important method involves using the left internal thoracic artery (LITA). The LITA normally originates from the left subclavian artery and courses along the anterior chest wall just lateral of the sternum. For this operation, the LITA is mobilized from the chest wall and, with its proximal origin left intact, the distal end is divided and sewn to the coronary artery beyond the site of occlusion (most commonly the left anterior descending coronary artery). After the LITA anastomosis is completed and any further arterial or vein grafts are completed, CPB is weaned as the heart resumes its normal rhythm. The cannulae are removed, temporary pacing wires are sewn to the heart, and plastic tubes are passed through the chest wall and positioned near the heart to drain any residual fluid collection. The two halves of the sternum are approximated using steel wire.
Because the traditional method of performing CABG involves significant operative trauma and morbidity to the patient, attention has been directed to developing less invasive surgical techniques that avoid splitting the sternum. The new techniques are performed with or without CPB through smaller incisions placed between the ribs. One method, called port-access, utilizes groin cannulation to establish CPB, while another, called minimally invasive direct coronary artery bypass or MIDCAB, is performed on the beating heart and therefore does not require CPB. Insofar as these techniques succeed in achieving less operative trauma compared to conventional CABG, postoperative pain is improved, the length of hospitalization is shortened, and the return to normal activity is hastened.
The port-access approach avoids the sternal splitting incision by employing femoral venoarterial CPB and an intraaortic (endoaortic) balloon catheter that functions as an aortic clamp by means of an expandable balloon at its distal end (Daniel S. Schwartz et al. xe2x80x9cMinimally Invasive Cardiopulmonary Bypass With Cardioplegic Arrest: A Closed Chest Technique With Equivalent Myocardial Protection.xe2x80x9d Journal of Thoracic and Cardiovascular Surgery 1996; 11 1:556-566. John H. Stevens et al. xe2x80x9cPort-Access Coronary Artery Bypass Grafting: A Proposed Method.xe2x80x9d Journal of Thoracic and Cardiovascular Surgery 1996; 111:567-573. John H. Stevens et al. xe2x80x9cPort-Access Coronary Artery Bypass With Cardioplegic Arrest: Acute and Chronic Canine Studies.xe2x80x9d Annals of Thoracic Surgery 1996; 62:435-441). This catheter also includes a separate lumen for the delivery of cardioplegic solution and venting of the aortic root. Alternatively, a different catheter may be placed percutaneously into the internal jugular vein and positioned in the coronary sinus for delivery of retrograde cardioplegic solution. Coronary bypass grafting is performed through a separate limited left anterior thoracotomy incision with dissection of the LITA and anastomosis to the atherosclerotic coronary artery under direct vision. Other bypass grafts to coronary arteries can be accomplished using radial artery sewn to the LITA. A description of port-access procedures is found in U.S. Pat. No. 5,452,733, the complete disclosure of which is incorporated herein by reference. Thus, the port-access approach focuses on avoiding the sternal splitting incision while maintaining a motionless heart to facilitate a precise coronary anastomosis as the primary means to reduce operative trauma and morbidity. Compelling evidence to support this contention, however, is scarce. Furthermore, no evidence exists regarding the effectiveness of the coronary anastomosis performed through the limited incision, nor the safety of the intraaortic balloon clamp and the vascular sequelae of groin cannulation. Finally, the port-access approach does not avoid the damaging effects of cardiopulmonary bypass, which include: 1) a systemic inflammatory response; 2) interstitial pulmonary edema; 3) neuropsychological impairment; 4) acute renal insufficiency; and 5) nonmechanical microvascular hemorrhage.
The MIDCAB approach also avoids the sternal splitting incision, favoring instead a limited left anterior thoracotomy incision (Tea E. Acuff et al. xe2x80x9cMinimally Invasive Coronary Artery Bypass Grafting.xe2x80x9d Annals of Thoracic Surgery 1996; 61:135-7. Federico J. Benetti and Carlos Ballester, xe2x80x9cUse Of Thoracoscopy And A Minimal Thoracotomy, In Mammary-Coronary Bypass To Left Anterior Descending Artery, Without Extracorporeal Circulation.xe2x80x9d Journal of Cardiovascular Surgery 1995; 36:159-61. Federico J. Benetti et al. xe2x80x9cVideo Assisted Coronary Bypass Surgery.xe2x80x9d Journal of Cardiac Surgery 1995; 10:620-625). Similarly, dissection of the LITA and anastomosis to the coronary artery are then performed under direct vision. The principal difference between the MIDCAB and port-access techniques, however, involves the utilization of cardioplegic solution and CPB (Denton A. Cooley, xe2x80x9cLimited Access Myocardial Revascularizationxe2x80x9d Texas Heart Institute Journal 1996; 23:81-84; and Antonio M. Calafiore et al., xe2x80x9cLeft Anterior Descending Coronary Artery Grafting via Left Anterior Small Thoracotomy without Cardiopulmonary Bypass,xe2x80x9d Annals of Thoracic Surgery 1996; 61:1658-65). Because MIDCAB is performed on the beating heart, cardioplegic solution, aortic cross-clamping and CPB are not required. This approach therefore focuses on the avoidance of cardiopulmonary bypass, aortic cross-clamping and the sternal splitting incision as the primary means to reduce operative trauma and morbidity after conventional CABG.
The potential advantages of MIDCAB compared to conventional CABG include: 1) the avoidance of CPB and aortic cross-clamping; 2) fewer embolic strokes; 3) less blood loss, hence a decreased transfusion requirement; 4) fewer perioperative supraventricular arrhythmias; 5) earlier separation from mechanical ventilatory support; 6) decreased or eliminated intensive care unit stay; 7) shorter length of hospitalization; 8) reduced total convalescence with earlier return to preoperative activity level; and 9) lower overall cost. Despite these potential benefits, however, the durability of the LITA to coronary artery anastomosis is uncertain. At the recent American Heart Association 69th Annual Scientific Session, the Mayo Clinic group reported on 15 patients undergoing MIDCAB. Of these 15 patients, three or 20% required reoperation to revise the anastomosis during the same hospitalization (Hartzell V. Schaff et al., xe2x80x9cMinimal Thoracotomy For Coronary Artery Bypass: Value Of Immediate Postprocedure Graft Angiography,xe2x80x9d Abstract presented at the American Heart Association, 69th Scientific Sessions, Nov. 10-13, 1996, Atlanta, Ga.). Of greater significance, however, was a report from Loma Linda University Medical Center that demonstrated a seven-year LITA to left anterior descending coronary artery patency rate of 42% in a subset of patients who underwent beating heart surgery and presented with recurrent angina. In contrast, the patency rate in an age-, sex- and disease severity-matched control group was 92% (Steven R. Gundry et al., xe2x80x9cCoronary Artery Bypass with and Without the Heart-Lung Machine: A Case Matched 6-year Follow-up,xe2x80x9d Abstract presented at the American Heart Association, 69th Scientific Sessions, Nov. 10-13, 1996, Atlanta, Ga.). Finally, because the MIDCAB approach is restricted mostly to patients with isolated disease of the left anterior descending coronary artery, the vast majority of patients with atherosclerotic heart disease are not appropriate candidates. Thus, despite the potential benefits of MIDCAB, its safety, efficacy, and applicability remain uncertain.
There are major obstacles to precise coronary anastomosis during MIDCAB. The constant translational motion of the heart and bleeding from the opening in the coronary artery hinder precise suture placement in the often tiny coronary vessel. Although bleeding can be reduced by using proximal and distal coronary occluders, by excluding diagonal and septal branches near the arterial opening when possible, and by continuous saline irrigation or humidified carbon dioxide insufflation, the incessant motion of the beating heart remains the Achilles heel of minimally invasive coronary artery bypass.
In summary, although port-access and minimally invasive direct coronary artery bypass techniques avoid the operative trauma and morbidity associated with the sternal splitting incision, both have serious disadvantages. The port-access approach is encumbered by the morbidity of cardiopulmonary bypass and aortic cross-clamping and the cost of the apparatus. Furthermore, the safety of the intraaortic balloon clamp and the vascular sequelae of groin cannulation are unresolved issues. The MIDCAB approach is imperiled by the constant motion of the beating heart which precludes a precise coronary anastomosis. Reports of poor graft patency rates and the need for early reoperation in a significant proportion of patients after MIDCAB attests to the technical difficulty of the procedure.
Conventional CABG requires arrest of the heart through the use of cardioplegic agents, aortic cross-clamping and cardiopulmonary bypass. These cardioplegic agents stop the beating heart to thereby allow precise suture placement and other surgical procedures. A mixture of magnesium sulfate, potassium citrate, and neostigmine has been used to induce cardioplegia during cardiopulmonary bypass. Sealy et al. xe2x80x9cPotassium, Magnesium, And Neostigmine For Controlled Cardioplegia: A Report Of Its Use In 34 Patients,xe2x80x9d Journal of Thoracic Surgery 1959, 37:655-59. Although both magnesium and potassium remain integral components of modern cardioplegic solutions, neostigmine was ultimately eliminated. Potassium citrate is currently the most commonly used cardioplegic agent. Potassium impedes excitation-contraction coupling, however, making it impossible to pace the heart by electrical stimulation and necessitating the use of a cardiopulmonary bypass system to sustain the patient. Other chemical agents that have been used in human cardiac operations to slow the rate of ventricular contraction include acetylcholine, neostigmine, adenosine, lignocaine, and esmolol. Another agent, carbachol or carbamyl choline, has been used to induce cardiac arrest in experimental animals. Broadley and Rothaul, Pflugers Arch., 391:147-153 (1981).
Acetylcholine has been used as a cardioplegic agent during cardiopulmonary bypass. Lam et al., xe2x80x9cInduced Cardiac Arrest In Intracardiac Procedures, An Experimental Study,xe2x80x9d Journal of Thoracic Surgery 1955; 30:620-25; Lam et al., xe2x80x9cClinical Experiences With Induced Cardiac Arrest During Intracardiac Surgical Procedures,xe2x80x9d Annals of Surgery 1957; 146:439-49; Lam et al., xe2x80x9cInduced Cardiac Arrest (Cardioplegia) In Open Heart Procedures,xe2x80x9d Surgery 1958; 43:7-13; and Lam et al., xe2x80x9cAcetylcholine-induced Asystole. An adjunct In Open Heart Operations With Extracorporeal Circulation,xe2x80x9d in Extracorporeal Circulation 1958, pp. 451-48; Lillehei et al., xe2x80x9cThe Direct Vision Correction Of Calcific Aortic Stenosis By Means Of A Pump Oxygenator And Retrograde Coronary Sinus Perfusion,xe2x80x9d Disease Of The Chest, 1956, 30:123-132; Lillehei et al., xe2x80x9cClinical Experience With Retrograde Perfusion Of The Coronary Sinus For Direct Vision Aortic Valve Surgery With Observations Upon Use of Elective Asystole Or Temporary Coronary Ischemia,xe2x80x9d in Extracorporeal Circulation, 1958, pp. 466-85; Lillehei et al., xe2x80x9cThe Surgical Treatment Of Stenotic Or Regurgitant Lesions Of The Mitral And Aortic Valves By Direct Vision Utilizing A Pump Oxygenator,xe2x80x9d Journal of Thoracic and Cardiovascular Surgery, 1958; 35:154-91. Conrad R. Lam, et al. Annals of surgery 1957; 146:439-49. Intravenous adenosine has been used to facilitate MIDCAB. M. Clive Robinson, First International Live Teleconference. Least-Invasive Coronary Surgery, The John Radcliffe Hospital, Oxford, England, Mar. 21 and 22, 1996.
Ventricular asystole has been achieved by direct injection of lignocaine into the interventricular septum. Khanna and Cullen, xe2x80x9cCoronary Artery Surgery With Induced Temporary Asystole And Intermittent Ventricular Pacing: An Experimental Study,xe2x80x9d Cardiovascular Surgery 1996; 4(2):231-236. Epicardial pacing wires were placed, and ventricular pacing was employed to maintain an adequate cardiac output. Esmolol has been used as a cardioplegic agent during cardiopulmonary bypass. Mauricio Ede et al., xe2x80x9cBeyond Hyperkalemia: B-Blocker-Induced Cardiac Arrest For Normothermic Cardiac Operations,xe2x80x9d Annals of Thoracic Surgery, 1997; 63:721-727.
In summary, there is a need for a surgical approach that avoids the risks and costs of cardiopulmonary bypass while preserving the benefits of a motionless operative field to achieve a precise coronary anastomosis. There is a further need for methods and compositions that enable predictable, controllable, transient arrest of the heart, which stop or slow the beating heart with acceptable half-life and quick onset of effect. There is a need for compositions and methods for transient arrest of the heart which can be used in a variety of medical and surgical procedures conducted on the heart, vascular system, brain, or other major organs, where pulsatile flow, movement associated with arterial pulsations, or bleeding is undesirable during the procedure.
Methods, compositions and apparatus are provided which are useful for diagnostic and therapeutic medical and surgical applications. The methods, compositions and apparatus are useful for cardiac surgery and other procedures, such as, for example, vascular and neurosurgery procedures, imaging procedures, robotically assisted surgical procedures, and procedures involving delivery of medical devices such as intravascular stents, bypass grafts, stent grafts, and occlusive/embolic devices (e.g., cerebral aneurysm coils), which may benefit from precise control of cardiac contraction, and/or minimized pulsatile flow and bleeding. Using the methods, compositions and apparatus disclosed herein for conducting a medical or surgical procedure, such as a coronary bypass, a substantially motionless operative field is provided.
In one embodiment, a method of performing a procedure on a human patient is provided, the method comprising: administering an effective amount of a composition capable of inducing reversible ventricular asystole to the patient, while maintaining the ability of the heart to be electrically paced; electrically pacing the heart with an electrical pacing system, thereby to maintain the patient""s blood circulation; selectively intermittently stopping the electrical pacing to allow ventricular asystole; and conducting the procedure during the time that the electrical pacing is intermittently stopped.
In another embodiment, a method of performing an aortic aneurysm repair procedure is provided in which a graft member is positioned within a region of a patient""s aorta, comprising inducing, prior to or during the repair procedure, at least one period of reversible ventricular asystole, while maintaining the ability of the heart to be electrically paced; wherein the period of asystole has a duration of more than approximately one minute. In one embodiment, the at least one period of reversible ventricular asystole is induced prior to or during positioning of the graft member in the aorta.
In another embodiment, a method of performing transmyocardial revascularization (TMR) is provided in which at least one blood flow channel is formed in a wall of the heart of a patient and is in fluid connection with a chamber of the heart. Prior to or during formation of the channel, at least one period of reversible ventricular asystole is induced, while maintaining the ability of the heart to be electrically paced, wherein the period of asystole has a duration of more than approximately one minute. The at least one blood flow channel, thus, may be formed during the period of asystole. In one embodiment, the blood flow channel in the heart is created by irradiating an exterior surface of the heart with laser energy. In another embodiment, the blood flow channel in the heart is created by irradiating an interior surface of the heart with laser energy.
In another embodiment, a method of imaging at least one intracorporeal aspect of a patient is provided comprising inducing, prior to or during image acquisition (of one or more images), at least one period of reversible ventricular asystole, and wherein at least one step of the image acquisition is performed during the period of asystole. The imaging procedure may be, for example, a CT scan or an MRI procedure. In another embodiment, the imaging procedure is echocardiography, comprising administering an ultrasonic probe to a patient for imaging an anatomical structure within the patient""s body by ultrasonic image acquisition. The echocardiography may be, for example, transesophageal echocardiography in which an ultrasonic probe is passed through a mouth of a patient and inserted into the patient""s esophagus for imaging an anatomical structure within the patient""s thoracic cavity by ultrasonic image acquisition.
In another embodiment, a procedure of introducing or inserting an occlusive material (which may comprise a substance(s) or a device) within a blood vessel of a patient is provided, comprising inducing, prior to or during the procedure, at least one period of reversible ventricular asystole. The material thus may be introduced or deployed during the period of asystole. In one embodiment, the at least one period of reversible ventricular asystole is induced prior to or during the deployment of the occlusive material. Where an occlusive device is used, it may comprise, for example, an intravascular coil. In one embodiment, the disease condition treated with the procedure may comprise an arteriovenous malformation. In another embodiment, the disease condition treated with the procedure may comprise an arteriovenous fistula. The occlusive material may be introduced into the blood vessel via a delivery catheter which is percutaneously introduced into the patient""s vasculature system.
In one embodiment, a method of performing a robotically-assisted surgical procedure is provided in which a practitioner uses one or more robotically-controlled devices to perform a surgical procedure within a body of a patient, comprising performing a robotically assisted procedure and inducing, prior to or during the robotically assisted procedure, at least one period of reversible ventricular asystole.
For the diagnostic and therapeutic medical and surgical procedures disclosed herein, the period of asystole may have a duration of, for example, about 3 to 20 minutes. In one embodiment, the period of asystole is induced by administering an AV node blocker and a xcex2-blocker to the heart at a sufficient dosage amount of each to induce asystole in the heart. The AV node blocker may comprise a cholinergic receptor agonist such as, for example, carbachol. The xcex2-blocker may comprise, for example, propranolol. In one embodiment, the method comprises electrically pacing the heart to maintain the patient""s blood circulation. The method may further comprise selectively intermittently stopping the electrical pacing during the asystole at least once during the procedure for an intermittent period, each of the one or more intermittent periods having a duration of, for example, about 1 to 30 seconds. In one embodiment, the xcex2-blocker is administered prior to the AV node blocker. The xcex2-blocker may be administered in an amount sufficient to substantially reduce the amount of AV node blocker required to induce asystole of the heart.
For the medical and surgical diagnostic and therapeutic procedures disclosed herein, the AV node blocker and the xcex2 blocker may be administered to the right or left coronary artery of the heart, for example, through a drug delivery catheter which has at least one discharge opening which is positioned in the right or left coronary artery. The discharge opening, in one embodiment, is positioned in the right coronary artery proximate to the AV node artery. The drug delivery catheter may be percutaneously inserted into the right coronary artery from a peripheral vascular access point, which may be, for example, a brachial artery, for example a femoral artery, for example a carotid artery, for example a radial artery.
For the medical and surgical diagnostic and therapeutic procedures disclosed herein, the propranolol may be administered as one or more bolus infusions at a total dosage amount of, for example, about 1 to 8 mg. The carbachol may be administered as one or more initial bolus infusions at a total dosage amount of, for example, about 0.001 to 1.0 mg per bolus. In another embodiment, the method comprises maintaining the period of asystole by administering a continuous intracoronary infusion of carbachol to the heart of the patient at a rate of, for example, about 0.001 to 0.3 mg/min over a time period of, for example, about 5 to 90 minutes.
In one embodiment, a system for performing a medical procedure on a patient is provided comprising: a drug delivery device; a transvenous pacing catheter; and at least one endoscopic instrument which is capable of performing a diagnostic or therapeutic interventional procedure within a vessel or bodily organ within the patient""s body. In one embodiment, the system further comprises at least one guide catheter. The drug delivery device may have a sufficient length and flexibility to allow transluminal positioning of the device into a right or left coronary artery of the heart of the patient from a peripheral access vessel. The transvenous pacing catheter may have a sufficient length and flexibility to allow transluminal positioning of the catheter into a right (or left) ventricle of the heart of the patient from a peripheral access vessel.
In one embodiment, the system further comprises an energy source coupled to the endoscopic instrument, wherein the energy source may be, for example, a laser energy source. The endoscopic instrument may comprise, for example, a flexible lasing apparatus, for example an endoscopic viewing device, for example a transesophageal echocardiographic probe, for example an endograft aortic prosthesis delivery catheter, for example a neurovascular stent delivery catheter, for example a neurovascular coil delivery catheter, for example an electrophysiologic mapping catheter, for example an ablation catheter, for example a stent delivery catheter, for example an angioplasty catheter.
In one embodiment, the system further comprises at least a first container comprising a dosage amount of an AV node blocker, which may be a cholinergic receptor agonist such as, for example, carbachol. The system may further comprise a second container comprising a xcex2-blocker such as, for example, propranolol.
In one embodiment, the system further comprises an electrical pacing system operatively coupled to the pacing catheter which may comprise, for example, an extracorporeal pacer, a switch remotely coupled to the pacer, and an actuator arranged remote from the pacer and coupled to the switch. In one embodiment, the actuator comprises a foot pedal.
The above is a brief description of some deficiencies in the prior art and advantages of the present invention. Other features, advantages and embodiments of the invention will be apparent to those skilled in the art from the following description, accompanying drawings and appended claims.